During leukemogenesis the neoplastic cells escape immunosurveillance. Certain nononcogenic viruses interfere with this process. The two major objectives of this research project are to investigate these phenomena. Antibody-producing B cells, thymus- dependent T cells involved in "cell-mediated immunity", and marrow- dependent M cells responsible for the rejection of allogeneic hemopoietic cells are all potentially capable of eliminating leukemic cells but fail to do so in genetically susceptible mice for various reasons. An inductive environment necessary for B cell differentiation is suppressed by both Friend virus and cortisol. Genetic studies and cell transfer experiments will be performed to characterize the environment, including a search for "suppressor cells". T cell functions are not impaired early by Friend virus, but erythroleukemic cells fail to stimulate allogeneic thymocytes in vitro as if mixed leukocyte culture-stimulation (MLR-S) antigens are not expressed. Various types of leukemic cells will be analyzed for expression of MLR-S antigens. Any interference with T cell function by Friend virus directly or by "suppressor cells" will be tested for using tissue culture techniques. The ability of leukemia to bypass M cells is puzzling, since Hemopoietic histocompatibility (Hh) antigens, which stimulate M cells, are well expressed on leukemic cells. M cells in general are not suppressed by Friend virus, and maturation of M cells and relative resistance to leukemia occur at the same time. "Tolerance" to Hh antigens during leukemogenesis will be tested for using cell transfer experiments. Possible mechanisms by which certain nononcogenic viruses prevent erythroleukemia caused by Friend virus will be investigated, with particular emphasis placed on their immunological effects. Such viruses will be tested for their therapeutic value in leukemic mice irradiated and grafted with bone marrow cells.